Important questions remain about the immunology and epidemiology of visceral leishmaniasis. A subset of infected persons develop overwhelming disease which progresses to death if they are not treated; others have asymptomatic, self-resolving leishmanial infection. Although many factors may contribute to the outcome of leishmanial infection, cell mediated immune mechanisms are almost certainly responsible for control of the parasite and protection against reinfection. Our goal is to characterize the natural history, epidemiology and immunology of American visceral leishmaniasis in residents of rural, northeastern Brazil where L. chagasi poses a major health problem. Leishmania-specific cellular and humoral immune responses will be assessed. Emphasis will be directed toward identifying parasite antigens which stimulate leishmania-specific T helper cells at sequential times during self- resolving, asymptomatic infection and to characterizing the relationship of those antigens to parasite antigens identified by immunoblots of serum. Similar studies will be performed in patients after successful treatment of symptomatic visceral leishmaniasis. The final aim is to isolate human T helper cell lines and clones which are dependent on leishmanial antigen for proliferation and lymphokine production in order to characterize the antigens to which these T cells respond. Completion of the proposed studies should provide important new insights into the epidemiology and immunology of American visceral leishmaniasis and a better understanding of the leishmanial antigens that elicit T helper cell responses.